Malaria and its conquering

Joel G. Breman, MD, DTPHFogarty International CenterNational Institutes of Health

Tropical Infectious Diseases WorkshopOswaldo Cruz Foundation (FIOCRUZ)

Rio de Janeiro, Brazil28 April–1 May 2003

Conquering Malaria

• Ecology and burden• Interventions• Successes• Economics• Research questions• Controversies

Ecology and Burden

Malaria and Ecology and Burden

Intrinsic and Extrinsic Factors

Controland prevention

measuresHuman

Parasite Mosquito

Social, behavioral, economic and

political factors

Environmental conditions

Malaria Ecology and BurdenClinical Manifestations

Infected Mosquito

Infected Human

Chronic effects

AnemiaNeurologic/ cognitiveDevelopmental

Impaired growth and development

Malnutrition

Acute febrile illness

Severe illness

Hypoglycemia

Anemia

Cerebral malaria

DeathRespiratory distress

Pregnancy

Fetus

MaternalAcute illness

AnemiaImpaired productivity

Low birth weight Infantmortality

Mendis K, Sina B J, Marchesini P, Carter R (2001) The neglected burden of P.vivax malaria. American Journal of Tropical Medicine and Hygiene 64; Supplement titled "The Intolerable Burden of Malaria: A New Look at the Numbers" 1-106.

Global distribution of Plasmodium vivax

maximum distribution 19th century (pink) late 20th century (purple)

MARA/ARMA Model of Malaria Transmission, 2003

Deaths and Malaria-related Deaths (1000s), 2000

Population All deaths (%)Malaria Deaths (%)

Malaria/total (%)

World 6,122,210 56,554 1,124 2.0

Africa 655,476 10,681 (18.9) 963 (85.7) 9.0Americas 837,967 5,911 (10.5) 1 (-) 0.02East Med. 493,091 4,156 (7.3) 55 (4.9) 1.3Europe 874,178 9,703 (17.2) 0 -SE Asia 1,559,810 14,467 (25.6) 95 (8.5) 0.7West Pacific

1,701,689 11,636 (20.6) 10 (0.9) 0

Disability–adjusted Life Years (DALYs, 1000s),All Cause and Malaria-related, 2002

PopulationDALYs fromall deaths (%)

DALYs from malaria deaths (%)

DALYs from malaria/total (%)

World 6,122,210 1,467,257 42,280 2.9

Africa 655,476 357,884 (24.4) 36,012 (85.2) 10.1

Americas 837,967 145,217 (9.9) 108 (0.2) 0.07

East Med. 493,091 136,221 (9.3) 2,050 (4.8) 1.5

Europe 874,178 151,223 (10.3) 20 (0.04) 0.01

SE Asia 1,559,810 418,844 (28.5) 3,680 (8.7) 0.9

West Pacific 1,701,689 257,868 (17.6) 409 (1.0) 0.2

0

500,000

1,000,000

1,500,000

2,000,000

2,500,000

3,000,000

Worldwide Africa Asia

Estimated World and Regional Malaria Deaths, 1952-1999

Disease

Malaria 57.9%Childhood Diseases 55.0%Diarrheal Diseases 53.2%Perinatal Conditions 45.0%Tuberculosis 44.4%Maternal Conditions 43.2%Respiratory Infections 42.6%

HIV/AIDS 41.8%Weighted Average 48.6%

Percentage of Deaths from Disease OccurringAmong the Poorest 20% of Global Population

% Deaths

Interventions

Estimated Cost of Malaria Control in an Endemic Area: One Million People, One Round

of Residual House Spraying

InsecticideOne application

(tons) Price/ton Total costCost per

capita

DDT 147 $3,950 $580,650 $0.58

Malathion 220 $4,300 $946,000 $0.95Deltamethrin 110 $20,000 $2,200,000 $2.20Pyrimiphos-methyl

220 $16,000 $3,520,000 $3.52

Estimated Cost of Malaria Control: One Million People, One Full-dose Treatment, 1999

Drug

Tablets in millions (dose)

Price/ 1000 tabs Total cost

Cost per

capita

Chloroquine (3 days)

11.25 (100 mg)

$6.05 $68,063 $0.08

Sulfadoxine-pyrimethamine (one dose)

2.5 (500 mgS/25 mgP)

$47.00 $117,500 $0.12

Quinine (7 d) 31.5 (300 mg) $41.25 $1,299,375 $1.30Artesunate (5 d) 13.5 (50 mg) $365.00 $4,927,500 $4.93

Successes

• 1899, (large scale) demonstration of successful Anopheline control in Cuba: antilarval and adult measures (large-scale)

• 1899–1914, multiple demonstrations of control by reduction of Anopheline larvae and adults– 1899, Sierra Leone (antilarval); Cuba (large-scale);

Malaysia (antilarval)– 1904–1914, Panama Canal Zone; control by

larviciding, large-scale environmental modification• 1927, elimination of A. albimanus in Barbados

(first area-wide success with invading species)

Successes

Successes (2)• 1935-1939, large-scale control by

pyrethrum spraying in South Africa, Netherlands and India

• 1939-1957– 1939-1940, Elimination of invading A.gambiae

from Brazil– 1942-1945, A.gambiae eliminated from

northern Egypt– 1946-1957, Interruption of transmission by

anti-mosquito measures in Cyprus, Sandinia, Guyana, Venezuela and Greece; indoor residual spraying with DDT, a major strategy

Successes (3)

• 1987-2003– Multiple projects and programs using

insecticide-impregnated bed nets demonstrate overall mortality reduction and decrease in several malaria indices

Interventions, Control and Economics

Type of ControlVector Control

• Environmental modification (urban)*• Chemical and biological larvicides*• Indoor residual insecticide spraying*• Outdoor residual insecticide spraying

*costly and effective

Type of ControlPersonal protection (2)

• Insecticide–impregnated materials:nets, curtains, clothing*

• House screening• House location• Repellents• Fumigants

* Shown cost effective for low-income countries

Type of ControlAntiplasmodial (3)

• Patient management: early diagnosis, treatment, referral, education

• Chemoprophylaxis• Intermittent treatment (pregnancy)*• Radical therapy for relapses (P.vivax,

P.ovale)

* cost effective

Type of ControlSocial Action

• Mobilization of individual, family, community• Health education

Management Effectiveness• Health systems effectiveness (quality),

efficiency• Leadership, planning, policies, strategies,

tactics• Surveillance• Monitoring and evaluation

Research Questions

Research Agenda

• Pathogenesis

• Drug development

• Vaccine development

• Diagnostics

• Clinical and community-based trials

• Entomology

Research Agenda (2)

• Clinical issues– anemia– neurologic and cognition– pregnancy-related

• Health services delivery

• Social, legal, ethical

Controversies

Controversies• Drugs

– Combination artemisinin-based compounds for treatment

– Chemoprophylaxis for high risk persons

• Burden– Malaria as a cause or risk-factor

(co-morbidity)– Cognition and developmental issues

Controversies (2)

• Transmission– Cost-effective vector control

approaches in urban and rural areas– Impregnated materials, how to improve

and make the social standard

• Basic research– Immunologic, genetic

Malaria, Annual WHO Estimates, 1997

RegionPopulation at risk (1000s)

Total Cases(%) (1000s)

P. Falciparum(%) (1000s)

P.vivax(%) (1000s)

SE Asia, Western Pacific

1,284,000 86,401 44,400 42,006

Eastern Mediterranean

64,600 14,539 2,883 11,656

Central America/ Caribbean

64,200 3,676 580 3,096

South America 23,500 11,325 3,347 7,978Central Asia/ Cancasus

8,480 167 0 167

World total outside Africa

1,444,780 116,334 51,211 65,124

Africa 550,000 300,000 Most of total 6-15,000Imported malaria² 1,590,000 33 11 22Total ³

Malaria in Sri Lanka

0

100000

200000

300000

400000

500000

600000

1963 1968 1973 1978 1983 1988 1993

Year

Num

ber o

f cas

es

0

10

20

30

40

50

60

P.falciparum

as % of total m

alaria

DDT spraying

endsFirst report of chloroquine

resistant P.falciparum

Plasmodium falciparumPlasmodium vivax

0.01

0.10

1.00

0.000 0.001 0.010 0.100 1.000 10.000

Annual malaria incidence rate (%)

Prop

ortio

n of

P.v

ivax

: :

% P

lasm

odiu

m v

ivax

100

10

1

Total Annual Malaria Incidence Rate (%)

0.000 0.01 0.001 0.1 1.0 10.0

0.01

0.10

1.00

0.000 0.001 0.010 0.100 1.000 10.000

Annual malaria incidence rate (%)

Prop

ortio

n of

P.v

ivax

: :

% P

lasm

odiu

m v

ivax

100

10

10.000 0.01 0.001 0.1 1.0 10.0 More Northerly,

more temperate

More Southerly, more tropical